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Biomedical subjects

M S Lubinsky

Publications and source records attributed to M S Lubinsky.

At least 19 recordsLinked to original sources
PubMed1998

A further report on a case of Floating-Harbor Syndrome in a mother and daughter.

We present the most extensive neuropsychological and language assessment yet reported of patients diagnosed with Floating-Harbor Syndrome (FHS), a rare genetic condition characterized by dysmorphid figures, short stature, and speech-onset delay. This is also the second reported occurrence of both a mother and daughter with FHS. Whereas the child demonstrated gross deficits in verbal expression, speech and language problems were largely ameliorated in the mother. Neuropsychological assessment also revealed a strikingly similar pattern of cognitive problems additional to language dysfunction, including difficulties with attention, mathematical, and visuospatial abilities. A mood disorder continued to be quite disabling for the mother.

Adult↗
PubMed1997

Classifying sex biased congenital anomalies.

The reasons for sex biases in congenital anomalies that arise before structural or hormonal dimorphisms are established has long been unclear. A review of such disorders shows that patterning and tissue anomalies are female biased, and structural findings are more common in males. This suggests different gender dependent susceptibilities to developmental disturbances, with female vulnerabilities focused on early blastogenesis/determination, while males are more likely to involve later organogenesis/morphogenesis. A dual origin for some anomalies explains paradoxical reductions of sex biases with greater severity (i.e., multiple rather than single malformations), presumably as more severe events increase the involvement of an otherwise minor process with opposite biases to those of the primary mechanism. The cause for these sex differences is unknown, but early dimorphisms, such as differences in growth or presence of H-Y antigen, may be responsible. This model provides a useful rationale for understanding and classifying sex-biased congenital anomalies.

Congenital Abnormalities↗
PubMed1997

Association of prenatal vascular disruptions with decreased maternal age.

Disruptions of fetal structures can create a variety of congenital anomalies. Some apparent prenatal vascular disruptions associate strongly with decreased maternal age, and are rare with older mothers. This is well-documented for gastroschisis, but similar findings with hydranencephaly suggest a general phenomenon that may also involve porencephaly, septo-optic dysplasia, early body stalk disruptions, certain hemifacial anomalies, and other findings. Prenatal vascular disruption may be a common cause of congenital anomalies, but its nature is unknown, and obvious environmental confounders associated with decreased maternal age may have only relatively small contributions. A protective effect for pregnancies of older mothers also remains a possibility.

Confounding Factors, Epidemiologic↗
PubMed1997

Decreased maternal age with hydranencephaly.

We studied parental ages of institutionalized children with hydranencephaly. Mothers under age 20 years and under age 18 years were, respectively, 5 and 10 times as frequent as in the general population, and 3 and 4 times more frequent than for institutionalized control patients. Unwed mothers were also common, but may reflect high rates in younger mothers combined with institutionalization bias. Thus, hydranencephaly appears to show a decreased maternal age effect, similar to that seen with other conditions presumably due to prenatal vascular disruptions.

Adolescent↗
PubMed1997

Hypothesis: septo-optic dysplasia is a vascular disruption sequence.

Septo-optic dysplasia, a variable combination of absence of the septum pellucidum, optic nerve hypoplasia, and pituitary abnormalities, makes little embryologic sense: components arise from different tissues and processes at different times, it is seen often with porencephaly, which is asymmetric, and rarely with other midline findings, genetic causes are exceptional, and occasional absence of the pituitary stalk is developmentally anomalous. Vascular vulnerabilities of components, anatomical overlap with findings of hydranencephaly and porencephaly, and a decreased maternal age effect similar to that of other abnormalities with presumed vascular origins, suggest a vascular disruption sequence instead, possibly involving the proximal trunk of the anterior cerebral artery.

Abnormalities, Multiple↗
PubMed1996

Duplication of the PMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1 neuropathy.

Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin gene PMP22. Clinical features of CMT1A include progressive distal muscle atrophy and weakness, foot and hand deformities, gait abnormalities, absent reflexes, and the completely penetrant electrophysiologic phenotype of symmetric reductions in motor nerve conduction velocities (NCVs). Molecular and fluorescense in situ hybridization (FISH) analyses were performed to determine the duplication status of the PMP22 gene in four patients with rare cytogenetic duplications of 17p. Neuropathologic features of CMT1A were seen in two of these four patients, in addition to the complex phenotype asociated with 17p partial trisomy. Our findings show that the CMT1A phenotype of reduced NCV is specifically associated with PMP22 gene duplications, thus providing further support for the PMP22 gene dosage mechanism for CMT1A.

Blotting, Southern↗
PubMed1994

von Voss-Cherstvoy syndrome: a variable perinatally lethal syndrome of multiple congenital anomalies.

We report 4 cases and review 7 from the literature with a pattern suggesting a variable early lethal multiple congenital anomaly syndrome. This was first reported by von Voss et al. [1979: "Klinische Genetik in der Pädiatrie," pp 70-74] and Cherstvoy et al. [1980: Lancet ii:485], and can affect upper limbs, face, brain, heart, lungs, urogenital and gastrointestinal systems, vertebrae and ribs, and can include thrombocytopenia. The initial cases had occipital encephaloceles and phocomelia, but milder cerebellar anomalies and radial ray defects may be seen instead. Both sexes are affected and parental age is not increased. This may be heterogeneous, but two consanguineous families, one with recurrences, suggest autosomal recessive inheritance in at least some instances, although the recurrences had milder brain findings than the other cases. The original designation of DK-phocomelia syndrome is inaccurate, since arm findings may be limited to radial anomalies; we suggest instead the von Voss-Cherstvoy syndrome. This may be heterogeneous, but at present, phenotypic overlap prevents differentiation of subgroups. The disorder appears to be part of a group of syndromes with radial and hematologic abnormalities.

Abnormalities, Multiple↗
PubMed1994

Linkage of a human brain malformation, familial holoprosencephaly, to chromosome 7 and evidence for genetic heterogeneity.

Holoprosencephaly (HPE) is a common malformation of the developing forebrain and midface characterized by incomplete penetrance and variable expressivity. Familial HPE has been reported in many families with autosomal dominant inheritance in some and apparent autosomal recessive inheritance in others. We have examined 125 individuals from nine families with autosomal dominant HPE. Expression in gene carriers varied from alobar HPE and cyclopia through microforms such as microcephaly or single central incisor to normal phenotype. We performed linkage studies by either Southern blot or polymerase chain reaction analyses with DNA markers (D7S22, D7S550, and D7S483) that are deleted from some patients with sporadic HPE and flank a translocation breakpoint in 7q36 associated with HPE. The strongest support for linkage was with D7S22, which was linked with no recombination to autosomal dominant HPE in eight of nine families with a combined logarithm of odds score of 6.4 with an affected-only model-free analysis and 8.2 with a reduced-penetrance model and all phenotypes. Close linkage to this region could be excluded in one family, and there was significant evidence of genetic heterogeneity. These results show that a gene for autosomal dominant HPE is located in a chromosomal region (7q36) known to be involved in sporadic HPE with visible cytogenetic deletions. They also demonstrate genetic heterogeneity in familial HPE. We hypothesize that mutations of a gene in 7q36, designated HPE3, are responsible for both sporadic HPE and a majority of families with autosomal dominant HPE.

Adolescent↗
PubMed1994

Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis.

A neonate with deficiency of branching enzyme (glycogenosis type IV) presented symptoms of severe hypotonia pre- and postnatally, and dilated cardiomyopathy in early infancy. The classical clinical manifestation of liver cirrhosis was not present, although amylopectin-like inclusions were found in the hepatocytes. In contrast to a previous report, the neurons in the brain stem and spinal anterior horns contained PAS-positive, diastase-resistant deposits. The combined involvement of the muscles and motor neurones could account for the severity of hypotonia. The muscle biopsy, electromyogram and biochemical and enzyme assays were helpful in establishing the diagnosis.

Biopsy↗
PubMed1993

GM1-gangliosidosis type 1 involving the cutaneous vascular endothelial cells in a black infant with multiple ectopic Mongolian spots.

GM1-gangliosidosis (GM1) is one of the metabolic storage diseases, of which a differential diagnosis requires an array of biochemical assays to determine the enzyme deficiency. This approach is not only time-consuming and costly but also unavailable to most hospital laboratories. However, a presumptive diagnosis of GM1 may be made on the basis of coarse facial feature, foamy endothelial cells in the cutaneous blood vessels and ectopic Mongolian spots, if present. A more definitive diagnosis of GM1 is then made on the demonstration of deficiency of GM1 beta-galactosidase in leukocytes, plasma or cultured skin fibroblasts. Thus, a battery of enzyme tests may be averted.

Black People↗
PubMed1991

Sir A. E. Garrod, congenital heart disease in Down syndrome, and the doctrine of fetal endocarditis.

Archibald Garrod was apparently the first to document congenital heart disease as a component of Down syndrome. This arose from his interest in fetal endocarditis, a theoretical cause of cardiac malformations, in vogue roughly from 1840-1940, that drew its strength from analogies with rheumatic heart disease in adults. Garrod's discovery sheds light not only on nineteenth century ideas about teratology, but also on his methodology, genius, and approaches that, in many ways, foreshadowed the techniques that guided his later work on inborn errors.

Down Syndrome↗
PubMed1991

Explaining certain human limb anomalies and the limb-hematopoiesis community of syndromes using a model of determination.

Disturbances of determination, the process of limitation of developmental potential, can cause structural as well as histologic anomalies. A polar coordinate model (PCM) developed from studies in animals, in which determination depends upon positional information arranged along polar coordinates, can be used to explain certain classes of human limb anomalies. Under the model, interference with this system primarily affects distal patterning. If the radial area is distal to the zone of polarizing activity in embryological development, as it appears to be, the PCM explains the teratologic equivalence of preaxial duplications and deficiencies in certain circumstances and the prevalence of ulnar dimelias in forearm duplications. Also, failures of hematopoiesis can be considered late problems with determination and may be markers for abnormalities of a determinative process that also has earlier developmental consequences. Abnormalities of retinoic acid morphogen receptors would be one possible mechanism. This would provide a rationale for the known association of postnatal hematologic problems with developmental anomalies preferentially affecting the radial area. Syndromes with limb and hematopoietic problems may well be a community of determinative disorders.

Abnormalities, Multiple↗
PubMed1987

Cat-eye syndrome with different marker chromosomes in a mother and daughter.

Except for atypical eye findings in the daughter, a mother and daughter with bisatellited marker chromosomes had abnormalities consistent with cat-eye syndrome. The mother's marker chromosome (mar number 1) is derived from one 22 and another acrocentric, possibly also a 22; the daughter's marker (mar number 2) may be an iso-dicentric, inv-dup (22) derivative of mar number 1. The mother has a tertiary trisomy translocation chromosome composed of at least one and perhaps two copies of 22pter----q11.2, whereas the daughter clearly has a secondary trisomy 22pter----q11.2 isochromosome, confirming this region as a cause of cat-eye syndrome. Results of hybridization using a unique sequence probe localized to 22q11 are consistent with the interpretation that both ends of both marker chromosomes are derived from 22.

Abnormalities, Multiple↗